Multiple myeloma MedDRA version: 21.0 Level: LLT Classification code 10028228 Term: Multiple myeloma System Organ Class: 100000004864
Conditions
Interventions
Product Name: JNJ-64007957
Product Code: JNJ-64007957
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Not Assigned
Curre
Sponsors
Janssen-Cilag International NV
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Each potential subject must satisfy all of the following criteria to be enrolled in the study: 1. =18 years of age. 2. Documented initial diagnosis of multiple myeloma according to International Myeloma Working Group (IMWG) diagnostic criteria 3. Must have either of the following: ? Received at least 3 prior lines of therapy (see definition below) including a PI (=2 cycles or 2 months of treatment) and an IMiD (=2 cycles or 2 months of treatment) in any order during the treatment (except for subjects who discontinued either of these treatments due to a severe allergic reaction within the first 2 cycles/months). OR ? Disease that is double refractory to a PI and an IMiD. For subjects who have received more than 1 type of PI, the disease must be refractory to the most recent one. Similarly, for those who have received more than 1 type of IMID, the disease must be refractory to the most recent one. 4. Measurable disease at Screening as defined by any of the following: ? Serum M-protein level =1.0 g/dL (in non-IgG myeloma, an M-protein level =0.5 g/dL);or ? Urine M-protein level =200 mg/24 hours; or ? Light chain multiple myeloma: Serum immunoglobulin free light chain =10 mg/dL and abnormal serum immunoglobulin kappa lambda free light chain ratio. 5. Eastern Cooperative Oncology Group (ECOG) performance status grade of 0 or 1 at Screening and at Cycle 1, Day 1 predose. 6. Clinical lab values as stated in the protocol 7. Women of childbearing potential must have a negative pregnancy test at screening and prior to the first dose of study drug using a highly sensitive pregnancy test either serum (ßhuman chorionic gonadotropin [ß-hCG]) or urine. 8. Women must be: a. Not of childbearing potential b. Of childbearing potential and – Practicing a highly effective, preferably user-independent method of contraception (failure rate of <1% per year when used consistently and correctly) and agrees to remain on a highly effective method while receiving study drug and until 100 days after last dose. – Agree to pregnancy testing (serum or urine) within 100 days after the last study drug administration. A woman using oral contraceptives must use an additional contraceptive method in addition to the requirements listed above. 9. Men must wear a condom when engaging in any activity that allows for passage of ejaculate to another person, during the study and for 100 days after the last dose of study drug. Male participants should also be advised of the benefit for a female partner to use a highly effective method of contraception as a condom may break or leak. 10. Women must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for at least 100 days after the last dose of study drug. 11. Men must agree not to donate sperm for the purpose of reproduction during the study and for at least 100 days after receiving the last dose of study drug. 12. Sign an informed consent form (ICF) indicating that he or she understands the purpose of and procedures required for the study and is willing to and able to participate in the study. Consent is to be obtained
Exclusion criteria
Exclusion criteria: Any potential participant who meets any of the following criteria will be excluded from participating in the study: 1. Treatment in the prior 3 months with an anti-CD38 therapy (eg, daratumumab), or discontinuation of a prior anti-CD38 therapy at any time due to an adverse event related to the anti-CD38 therapy. 2. Prior antitumor therapy as follows, before the first dose of study drug: • Targeted therapy, epigenetic therapy, or treatment with an investigational drug or an invasive medical device within 21 days or at least 5 half-lives, whichever is less. • Monoclonal antibody treatment within 21 days (anti-CD38 treatment cannot be used within the prior 3 months • Cytotoxic therapy within 21 days. • PI therapy within 14 days. • IMiD therapy within 7 days. • Radiotherapy within 21 days. However, if the radiation portal covered =5% of the bone marrow reserve, the subject is eligible irrespective of the end date of radiotherapy. • Gene modified adoptive cell therapy (eg, chimeric antigen receptor modified Tcells, NK cells) within 3 months 3. A cumulative dose of corticosteroids equivalent to =140 mg of prednisone within the 14-day period before the first dose of study drugs 4. Live, attenuated vaccine within 4 weeks prior to the first dose of study drug. 5. Toxicity from previous anticancer therapy that has not resolved to baseline levels or to Grade =1 (except alopecia or peripheral neuropathy). 6. Stem cell transplantation: • Allogeneic stem cell transplantation =6 months before the first dose of study drug. • Active graft-versus-host disease. • Autologous stem cell transplantation =12 weeks before the first dose of study drug. • An immunosuppressive drug (eg, cyclosporine, tacrolimus) within 28 days before the first dose of study drug. 7. Central nervous system involvement or exhibits clinical signs of meningeal involvement of multiple myeloma. If either is suspected, whole body magnetic resonance imaging (MRI) and lumbar cytology are required. 8. Active plasma cell leukemia (>2.0 x 10^9/L plasma cells by standard differential), Waldenström’s macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes), or AL amyloidosis. 9. Seropositive for human immunodeficiency virus. 10. Seropositive for hepatitis B (defined by a positive test for hepatitisB surface antigen [HBsAg]). Subjects with resolved infection (ie, subjects who are HbsAg negative but positive for antibodies to hepatitis B core antigen [Anti-HBc] and/or antibodies to hepatitis B surface antigen [Anti-HBs]) must be screened using real-time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) DNA levels. Those who are PCR positive will be excluded. EXCEPTION: Subjects with serologic findings suggestive of HBV vaccination (Anti-HBs positivity as the only serologic marker) AND a known history of prior HBV vaccination, do not need to be tested for HBV DNA by PCR. 11. Seropositive for hepatitis C (except in the setting of a sustained virologic response [SVR], defined as aviremia at least 12 weeks after completion of antiviral therapy). 12.
Design outcomes
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Serum concentrations and pharmacodynamic markers 2. Presence of anti-drug antibodies 3. Overall response rate 4. Clinical benefit rate (minimal response or better) 5. Duration of and time to response ; Timepoint(s) of evaluation of this end point: 1. Serum concentrations- Predose, Day (D) 1 of each cycle, End of treatment (EOT), follow-up Pharmacodynamic markers- Part 1: Cycle (C) 1 D1, C1D9, C1D10, C1D11, C1D12, C1D15, C1D16, C1D22, C2D1, C3D1,C7D1 Pharmacodynamic markers- Part 2: C1D1, C1D9, C1D11, C1D15 2. Part 1 and Part 2 (Serum and Plasma): C1D1, C2D1, C4D1, C7D1, EOT, Post-treatment follow-up 3. Duration of the study 4. Duration of the study 5. Duration of the study | — |
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objectives are: ? Part 1: To identify recommended Phase 2 doses and schedules (RP2Ds) for each combination ? Part 2: To characterize the safety of each RP2D for each combination ; Secondary Objective: The secondary objectives are: ? To characterize the pharmacokinetics and pharmacodynamics of each study treatment ? To assess the immunogenicity of each study treatment ? To evaluate the antitumor activity of each combination ; Primary end point(s): 1. Frequency and severity of dose-limiting toxicities 2. Frequency and severity of adverse events and serious adverse events ; Timepoint(s) of evaluation of this end point: 1. Cycle 1 (28 days) 2. From the time of signing the ICF till 100 days after the last dose of study drug or until the start of subsequent systemic anticancer therapy, if earlier. | — |
Countries
Netherlands, Spain, United States
Contacts
Public ContactGlobal Clinical Operations Spain
Janssen-Cilag SA
Outcome results
None listed